OCULAR MANIFESTATIONS OF LEPROSY

AND ITS MANAGEMENT

DISSERTATION SUBMITTED FOR

MASTER OF SURGERY DEGREE

BRANCH – III - OPHTHALMOLOGY

MARCH 2009

THE TAMILNADU

DR.M.G.R. MEDICAL UNIVERSITY

CHENNAI, TAMILNADU

Dept. of Ophthalmology,Govt. Rajaji Hospital,Madurai.

CERTIFICATE

This is to certify that this dissertation entitled “OCULAR

MANIFESTATIONS OF LEPROSY AND ITS MANAGEMENT”

has been done by DR. S.S. SUBHA under my guidance in

Department of OPHTHALMOLOGY, Madurai Medical College,

Madurai.

I certify regarding the authenticity of the work done to

prepare this dissertation.

DR.P. THIAYAGARAJAN.M.S.,D.O.,

PROFESSOR & H.O.D.DEPARTMENT OF OPHTHALMOLOGYGOVT. RAJAJI HOSPITAL &

MADURAI MEDICAL COLLEGEMADURAI.

DECLARATION

I, Dr. S.S. SUBHA solemnly declare that the dissertation

titled “OCULAR MANIFESTATIONS OF LEPROSY AND

ITS MANAGEMENT” has been prepared by me.

This is submitted to The Tamil Nadu Dr. M.G.R. Medical

University, Chennai, in partial fulfillment of the requirement for

the award of M.S.,(Ophthalmology) Branch-III degree

Examination to be held in MARCH 2009.

Place : Madurai

Date : Dr. S.S. SUBHA

ACKNOWLEDGEMENT

I am deeply indebted to Dr. P. THIYAGARAJAN. MS., D.O,

Professor and Head of the department of Ophthalmology,

Madurai Medical college, Madurai for the able guidance,

inspiration and encouragement he rendered at every stage of this

study.

I acknowledge with gratitude the dynamic guidance and

persistent encouragement given to me by my guide Dr. A.R.

ANBARASI, M.S., DO, Assistant Professor in Ophthalmology,

Department of Ophthalmology, Madurai Medical College,

Madurai for having taken keen interest in sharing her ideas

throughout the study period. Her valuable suggestions and patronage

has been a driving force to make this endeavor possible.

My Sincere thanks to Dr. Dr.M. SIVAKUMAR, M.D., Dean,

Madurai Medical College, & Govt Rajaji Hospital,, Madurai for

permitting me to utilize the clinical materials of the hospital.

Last, but not the least, my profound gratitude to all the

‘patients’, to whom I owe everything because, this venture would not

have been possible with out them.

CONTENTS

S.NO. TOPIC PAGE NO.

PART – 1

1. INTRODUCTION 1

2. MYCOBACTERIOLOGY 3

3. HISTORICAL BACKGROUND 5

4. EPIDEMIOLOGY 7

5. CLASSIFICATION 9

6. CLINICAL FEATURES OF LEPROSY 10

7. IMMUNOPATHOLOGY OF LEPROSY 26

8. MANAGEMENT 40

PART - II

1. AIM OF THE STUDY 49

2. MATERIALS & METHODS 50

3. PROFORMA

4. RESULTS & ANALYSIS 54

5. DISCUSSION 67

6. CONCLUSION 70

BIBLIOGRAPHY

MASTER CHART

INTRODUCTION

Hansens disease is a granulomatous infectious disease caused by

Mycobacterium leprae. It affects mainly peripheral nerves but it can also

affect skin, muscles, eye, bone, testes and internal organs.

Although much improved in last 25 years, knowledge of the

pathogenesis, course, treatment and prevention of the disease continues to

evolve. The skin lesions and deformities were historically responsible for

stigma attached to the disease. The introduction of MDT in early 1980 had

begun to have an impact on the transmission of disease and severity of its

attending complications.

Eye involvement in leprosy is quite common. Its complications,

particularly sight threatening complications, if neglected will lead to

blindness.

Good vision is required not only for performance of routine

activities but also for the care of anaesthetic hands and feet. Loss of

eyesight in a person who already have anaesthesia in hands and feet is a

disaster.

Ocular lesions range from chronic irritation of eyes to blindness. The

incidence of eye involvement in leprosy is stated to be anywhere from 15

% (tuberculoid) to 100% in long standing lepromatous leprosy.

Ocular involvement had been seen even in patient who have

completed the MDT. Every year, approximately 5.6% of patients with

multibacillary leprosy who completed MDT can be expected to develop

new ocular complications of leprosy which often (3.9%) are potentially

vision threatening. Similarly complications can occur during MDT

therapy and during relapse of the disease.

Ocular morbidity like orbicularis weakness and lagophthalmos are

found to be more in patients with reversal reaction. Elderly, deformed, skin

smear positive lepromatous patients are associated with increased ocular

morbidity and form a group that require acceptable and accessible eye

care.

This study aims at determining the incidence of various ocular

manifestations of leprosy and its management.

MYCOBACTERIOLOGY

MORPHOLOGY :

Mycobacterium leprae belongs to Actinomycetales and family

Mycobacteriaceae which are rod shaped aerobic and non sporing bacteria.

The organism does not stain readily but once stained they resist

decolourisation by acid or alcohol and hence called acid-fast bacillus. It

occurs singly in parallel bundles or in globular masses and often found

within endothelial cells of blood vessels, in mononuclear cells or in

schwann cells and is the only mycobacterium that infects peripheral

nerves. Its long generation time (12-13 days) is responsible for chronicity.

The bacteria involves cooler tissues of the body such as skin, superficial

nerves, nose, pharynx, eyes and testicles. This organism was described

by Armauer Hansen in 1873 .

CULTIVATION :

It has not been cultivated on non-living bacteriological media.

(Dasypus novemcintus) the nine branded armadillo is susceptible to

mycobacterium leprae possibly because it has a low body temperature.

About 40% of Armadillos inoculated with Mycobacterium leprae develop

florid lepromatous leprosy, both clinically and histopathologically after a

year or more.

However real break through was discovered by Shepard (1960) that

leprae bacilli could multiply in footpad of mice kept at low temperature20

degree Celsius. Following intradermal inoculation into footpad of mice, a

granuloma develops at the site in 1-6 months.

This technique had been utilized in diagnosis of the disease,

evaluation of potency of antileprosy drugs and detection of viability of the

bacilli during treatment.

One of the best known reports of cultivation is from Indian cancer

research center Bombay where AFB was isolated from leprosy patients

employing fetal ganglion cell culture.

Resistance :

Lepra bacilli is found to remain viable in a warm humid

environment for 9-16 days and in moist soil for 46 days. They survive

exposure to direct sunlight for 2 hours and UV rays for 30 minutes.

HISTORICAL BACKGROUND

The history of mans relationship with leprosy has always

invoked a great deal of speculation.

Word leper is derived from Greek language. The word leper

means scaly. The disease is thought to have had its origin in Asia. The

earliest records of leprosy like disease is from India and China as early as

600 B.C. In India leprosy has been known since ancient times as kustha

roga (in Sanskrit). Chaulmoogra oil was used as treatment for kustha roga.

The earliest evidence of leprosy is the mummies of second century B.C.

The disease probably was carried from India to Europe in fourth century

B.C by the returning Greek soldiers. From Greece, the disease spread

slowly throughout Europe where the maximum period of activity was

between tenth and fifteenth centuries. Subsequently the disease underwent

a steady and significant decline to 1/1,00,000 by the year 1900, due to the

strict isolation of patients and improvement in the quality of life of the

people .

For a long time the disease was thought to be a curse or punishment

from God. It was only after several centuries that the causative organism-

Mycobacterium leprae was discovered by Armauer Hansen of Norway in

1873, yet there was no effective remedy for the disease . For long time the

only way to handle leprosy patients was to isolate them for life in special

situation. With the introduction of sulfone drugs in the treatment of

leprosy in 1943 marked the beginning of new era- the era of case finding

and domiciliary treatment

With this and the magnitude of the disease in our country in mind, the

government of India launched the National Leprosy Control Programme

(NLCP) in 1955.

The development of experimental animal models occurred in 6o and

70”s. In 1960 – Shepard discovered M.leprae could multiply to certain

extent when injected into footpads of mice .In 1971 Krichheimer in USA

paved the way for vast experimental work in leprosy research. He reported

that armadillos developed disseminated leprosy when injected

experimentally with M.leprae.

Thus NLCP in India was redesigned as NLEP (National Leprosy

Eradication Programme) in 1983, with the goal of arresting the disease, by

the start of twenty first century.

EPIDEMIOLOGY

The evolution of leprosy as a disease has been slow that its

epidemiological pattern, probably extending over several centuries was

poorly documented than acute disease such as plaque worldwide.

The disease and its various clinical forms is not uniformly

distributed. The disease had died out completely in Northern Europe,

Hawai, Japan, Venezuela, United States of America. This is due to

economic development in these countries leading to change in risk factors.

It is still endemic at a low level in part southern and Eastern Europe, South

east Asia, Africa and Western pacific where poverty and low standard of

living still persist. Estimated number of cases is about 10-12 million.

Accurate assessment is not possible because the endemic population are

those of developing countries where reporting systems are poor.

Leprosy :

Leprosy is a major health problem in India. According to WHO

expert committee, a public health problem is said to exist when the

prevalence of leprosy is around 1/4000 population.

In 1981 number of cases is about 4 million. Prevalence being 5.7 /1000

population. Almost all states in India have a leprosy problem, there is a

great degree of variability. The disease is more prevalent in southern and

eastern regions than in northern region of the country. States maximally

affected are Tamilnadu, Pondicherry, Bihar and Orissa with prevalence

being >5/1000 population.

Ocular complications occur in 10%-90% of patients and probably

occur more frequently during leprosy than in any other systemic infectious

disease. Approximately 5% - 10% of patients with ocular leprosy are

blinded by the disease and a million or more leprosy patients have

substantial vision loss from leprosy.

CLASSIFICATION

Leprosy has been classified based on clinical, bacteriological,

immunological and historical status of patients. The following are various

classification:

Indian classification :

Indeterminate type

Tuberculoid type

Borderline type

Lepromatous type

Pure neuritic type

Matrid classification :

Indeterminate

Tuberculoid- flat : raised

Borderline

Lepromatous

Ridley and jopling classification :

According to their position on immunological scale it is divided into

Tuberculoid (TT)

Borderline tuberculoid (BT)

Borderline (BB)

Borderline lepromatous(BL)

Lepromatous type (LL)

The Indian and matrid classification systems are the most

widely used classifications in leprosy field programmes, whereas Ridely

and Jopling classification can be used only when full research facilities are

available.

CLINICAL FEATURES OF LEPROSY

Cardinal signs of leprosy :

Mycobacterium leprae (causitive organism)

↓

Affinity to nerves

↓

Inflammation

↓

Enlargement and tenderness of nerves

↓

Further inflammation → loss of nerve tissues → loss of function

↓

Sensory fibers are affected first leading to loss of sensation in the skin

lesion (or) in the area supplied by the nerve.

Atleast any one of the above three signs must be there to diagnose leprosy.

Leprosy by WHO case definition :

A person having one / more of the following features

1) Hypopigmented / reddish skin lesions with definite loss of sensation

2) Involvement of peripheral nerves as demonstrated by definite

thickening with loss of sensation.

3) Skin smear positive for AFB

Systemic features :

Mycobacterium leprae regardless of the route of entry into human

body, only a proportion of persons infected develop signs of the disease

after the incubation period of 3-5 years. Majority will develop sub-clinical

infection. The initial sites of infection are the peripheral nerves with target

organ being schwann cell. Thus the most common first symptom is a small

but persistent area of impaired sensation/numbness. In others, first

noticeable feature may be macules which are usually hypopigmented and

erythematous .

Tuberculoid leprosy :

Skin lesion :

It is documented by few (usually 3) solitary lesions affecting skin and

peripheral nerves. The margins are usually well defined, with dry and

rough surface. The lesions are firm in consistency. There is no central

healing. It is usually associated with loss of hair, loss of sweating and

anaesthesia. Lesions are usually asymmetrical.

Nerve lesions : Nerve involvement is common in this type of

leprosy. Nerves close to the skin lesion are usually affected. Nerve

abscess are more common. Systemic involvement is less common.

Lepromatous leprosy :

Skin lesions :

Lesions are ill defined, multiple, with smooth surface and soft in

consistency. Lesions are usually symmetrical.

Nerve involvement :

Nerve involvement occurs in late stage. Multiple nerves are affected.

Systemic involvement :

Systemic involvement is more common and severe in lepromatous

leprosy. Eye , nose , larynx and testes are involved .

Ocular features of leprosy :

Blindness is common and disastrous complication in leprosy. In 1873

Hansen stated “There is no disease which so frequently gives rise to

disorders of the eye as leprosy does”. The ocular adenexa and anterior

segment of the eye offer an ideal site for the proliferation of M.leprae. The

cooler temperatures, the presence of a rich neurovascular network and the

possibility of ocular immunologic compartmentalization may all be

incriminated as contributing to ocular complication during leprosy. Ocular

complications occur in 1/3 of leprosy patients.

For simplicity ocular lesions are classified into two groups. The first

group include potentially sight threatening lesions (PST) which includes

lagophthalmos and its sequelae, chronic iridocyclitis and its sequelae.

Lesions such as loss of eyebrows and eyelashes have no visual significance

but contribute to the stigma which these patients endure.

Process by which eye can be damaged :

1) Exposure and anaesthesia :

Involvement of occipital, temporal and zygomatic branches of the

facial nerve produce selective paralysis of orbicularis oculi muscle.

This is usually seen to occur during type I reactions and in untreated

lepromatous leprosy on later stages.

Bacillary infiltration of the superficial muscles of the face also

cause weakness in lepromatous leprosy. Lagophthalmos develops and

blinking is incomplete. Cornea and conjunctiva become prone to

drying and to minor trauma. In tuberculoid lesions of face, entropion

and trichiasis develops due to scarring of the tarsal plate.

2) Bacillary invasion :

Bacillary invasion of the eye occurs through both the blood

stream and via the corneal nerves, thus mainly involving cornea and

ciliary body.

3) Hypersensitivity :

Iris and ciliary body that have been involved by the leprosy

bacilli are prone to severe damage during type 2 lepra reaction. These

may be the sites of deposition of circulating immune complexes even

when there is no bacilli.

Ocular manifestations of leprosy :

Eyebrows - Madarosis

Lids - Lagophthalmos

- Entropion

- Ectropion

- Trichiasis

- Lid nodules

Meibomian glands - Tear film abnormalities

Lacrimal glands - Acute and Chronic

Dacryoadenitis

Sclera - Scleritis

- Episclerits

Cornea - Hypesthesia

- Avascular keratitis

- Corneal leproma

- Interstitial keratitis

Iris and ciliary body - Acute and Chronic

- Iridocyclitis

- Iris leproma

Lens - Complicated cataract

Raised IOP - Secondary open angle Glaucoma

Posterior segment - Choroidal and retinal pearls

- Choroiditis

External adenexal involvement :

Eyebrows :

Thinning of eyebrows and subsequent loss is one of the most

common manifestations of leprosy. This begins temporally and progresses

nasally probably because temporal brow is relatively cooler. Brow loss

may be total and permanent.

Eyelids :

Seventh nerve palsy results in lagophthalmos, lower lid ectropion,

occasionally upper lid entropion and poor lacrimal drainage. All leprosy

patients regardless of their clinical disease are at at risk of developing

lagophthalmos. Paucibacillary patients and those in reversal reaction

develop paralytic lagophthalmos earlier and suddenly. Multibacilary

patients develop paresis later in the disease and often also develop

anaesthesia of cornea and conjunctiva due to involvement of trigeminal

nerve.

Fifth and seventh nerve involvement leads to exposure

keratitis(neuroparalytic and neurotrophic), dry eyes, dermalization of

cornea and conjunctiva. Trichiasis, susceptibility to trauma resulting in

corneal scarring and blindness.

Eyelid nodules and placoid lesions develop in paucibacillary,

reversal, ENL reaction. There is a positive correlation between type 1

reaction lesions on the face and subsequently lagophthalmos which may

identify those patients who are at risk of developing corneal blindness

from exposure keratitis. Loss of skin elasticity, infiltration of marginal and

pretarsal fibers of orbicularis oculi muscle by M.leprae and loss of muscle

tone contributes to dermatochalasis and heavy drooping upper lids.

Further atrophy at the canthal tendons and tarsal plates creates heavy

floppy lids allowing ectropion perhaps entropion and trichiasis.

Meibomian gland :

Meibomian gland infiltration leads to atrophy and inadequate lipid

production with associated tear dysfunction.

Lacrimal gland and lacrimal sac :

Acute and chronic dacryoadenitis arising from cellular infiltration

and inflammation of lacrimal gland may occur in lepromatous leprosy. In

tuberculoid lesion, denervation of gland results in keratoconjuntivitis sicca

Severe nasal infiltration and mucosal scarring lead to NLD obstruction

and subsequent dacryocystitis in lepromatous patients.

Cornea :

M.leprae invades cornea through rich network the rich network of

limbal ciliary nerves during early stage. Hematogenous spread occur later

by way of blood vessels of corneal pannus.

Corneal hypesthesia may be found in all forms of the disease and

may lead to inadequate blink reflex which coupled with lagophthalmos,

ectropion and dry eyes leads to typical inferior exposure

keratoconjunctivitis . This is an early warning sign of inadequate

protection and increased risk of bacterial corneal infection and may leading

to blindness.

Enlarged edematous cornea nerves are found in lepromatous leprosy.

The nerve involvement has the appearance of focal swelling resembling

“bead of string “and consists of M.leprae and a surrounding

granulomatous response within the cranial nerve.

These nerve swellings are pathognomonic of leprosy and may be the

first sign of ocular and systemic leprosy. The nerve changes represent

granulomatous reactions that resolve spontaneously. Following treatment

lesions sometimes calcify and persist. Later it leads opacification of

cornea.

Avascular keratitis is characterized by the development of chalky

white punctate subepithelial opacities that are first seen in superior

temporal quadrant near the limbus. They are usually found in

asymptomatic non-inflammed eye.

Historically the lesion represents miliary lepromas and consists of

macrophages packed with leprae. The lesion becomes gradually confluent

and less demarcated causing surrounding cornea hazy. Later there is a

destruction of bowmans layer and superficial vascularisation produces the

classical lepromatous pannus.

Corneal lepromas appear as large white or yellowish nodules at the

limbus. They represent large granulomata and are relatively infrequent

except in Japan and South America. They occasionally encroach upon the

visual axis.

Interstitial keratitis begins in superotemporal quadrant and represent

a more severe form of avascular keratitis that progresses to necrosis and

later avascular invasion.

Sclera :

Nodular episclerits and scleritis usually consists of focal leproma

and an inflammatory response. Diffuse episcleritis and scleritis may also

occur as an immunologically driven disease with immune complex

deposition without direct bacillary invasion. It is typically observed during

lepra reactions and is often associated with keratitis or iridocyclitis.

Chronic / recurrent scleritis may lead to scleral necrosis, scleral melting

and staphyloma.

Iris and ciliary body :

Uveal tract involvement is primarily seen in lepromatous leprosy

and its incidence is directly proportional to disease duration.

Lepromatous iridocyclitis :

It may be 1) Caused by direct invasion of M.leprae into ocular

structures, hematogenous or by the way of ciliary nerves.

2) Neuroparalytic - as a result of early involvement of iris sympathetic

nerves.

Evidences for neuroparalytic iritis are :

1) Organismal :

a) Preferential attachment of lepra bacilli to nerves in various

organs, a similar manner of affliction may occur in iris.

b) Preferential lodgement of organisms in cooler parts of the

body (testes, nose ,ear). As iris temperature is 3.6 degree less

than the body temperature (Schwartz – 1962) it can be

preferential site.

2) Clinical :

a) Sluggishly reacting pupils with anisocoria without overt signs of

uveitis goes in favour of neuroparalytic basis.

b) Corneal nerve involvement is a well known clinical entity in

leprosy. A parallel situation might occur in iris.

3) Pharmacological :

a) Early autonomic denervation hypersensitivity has been described

by Bauschard and Swift (1972) in which pupils of lepromatous patients

responded positively to epinephrine in an abnormal way.

b) Poor response to anticholinergic drugs like atropine as the basic

fault lies in adrenergic nerve fibres.

4) Histopathological :

Lack of organisms in aqueous / iris and functional changes are

much more marked as compared to organic iris changes.

A uveal hypersensitivity to M.leprae has been isolated from normal

appearing eyes and it has been that iris is a site in which M.leprae might

survive long after skin smears have become negative. Early subtle

involvement includes diminished pupillary reactions, denervation

hypersensitivity to adrenergic agents and reduced accommodation.

Iris involvement can be divided into

1) Acute diffuse plastic iridocyclitis :

Acute non-granulomatous iridocyclitis is a common often

bilateral accompaniment of type 2 reaction. Its clinical presentation is

similar to other non- leprous iritis. The course of the disease is often

fulminant with a sudden painful onset, conjuctival hyperemia, keratic

precipitates, aqueous cells often with hypopyon formation , posterior

synechiae and secondary glaucoma. Spontaneous hyphaema may also

occur as a result of fragility of iris vasculature.

2) Chronic iridocyclitis :

The more common chronic iridocyclitis is less dramatic but

potentially blinding. It is a low grade granulomatous or non-

granulomatous iridocyclitis common in lepromatous leprosy but also

seen in tuberculoid form. It is characterized by a lack of symptoms and

overt signs. Although slit lamp examination may show aqueous cells

and flare with keratic precipitates scattered all over corneal

endothelium. Its chronic course leading to iris atrophy and polycoria.

Iris adhesions progress to seclude and occlude the pupil. Small non-

reacting pupils caused by the involvement of sympathetic iris nerves,

exaggerate visual impairment created by developing lens changes and

corneal opacities.

The presumed pathogenesis of chronic lepromatous iritis is that

during primary bacteremia, bacilli lodge in autonomic fibres of iris and

cause a slow degeneration of nerves which cause a muscular atrophy .

Due to atrophy of muscular toxins are released which causes a low

grade uveitis with mild flare, KP’s and cells with eyes remaining

essentially white and asymptomatic.

3)Miliary iris lepromas :

There are small glistening white lesions which are pathgnomonic

for leprosy. They represent aggregates of tightly packed living and dead

bacilli lying within mononuclear cells. Iris pearls usually develop

within a year or two of the commencement of iritis with little

accompanying inflammation or foreign body reaction.

Iris pearls are situated mainly at the papillary margin around the

collarette resembling a necklace. Pearls may also develop in slowly

increase in size and may tend to aggregate. They become pedunculated

and may eventually drop in AC where they are well tolerated and

produce no reaction.

4) Nodular iris lepromas :

Bacterial invasion of the iris may also give rise to the formation

of nodular leproma which are yellow globular polymorphic masses that

occur less commonly than the iris pearls. They occur rarely disrupt the

architecture.

5) Iris atrophy :

In lepromatous leprosy the so called chronic iritis produces iris

atrophy with small non-reacting pupils which exaggerate the visual

impairment created by developing lens changes and corneal opacities.

The cause of this chronic iritis is believed to be neuroparalytic from

early involvement of the small nerves of the iris particularly autonomic

supply.

Histopathology discloses far more silent chronic iridocyclitis

in leprosy patients that are diagnosed clinically. AFB can persist in this

tissue even after completion of MDT. Smooth muscle disruption and

destruction a cause of miotic pupil in leprosy has been conclusively

demonstrated histopathologically. Iris atrophy continues to develop in

3% patients with multibacillary leprosy. Every year after they complete

2 year course of MDT and is associated with age, increasing loads of

mycobacteria, sub-clinical cataract and corneal opacity.

6. Posterior segment lesions :

Uveitis in leprosy spares choroids because organisms predilection

for cooler parts of the body. Rarely choroidal pearls and retinal pearls

in posterior pole affecting vision has been described. Chorioretinal

involvement can be in the form of proliferation of RPE, hypopigmented

patches, peripheral non- specific choroiditis, disseminated choroiditis,

as well as colloid degeneration in the macula. These are non-specific

and are the result of reaction to the sensitized uveal tract.

Ocular complications :

Ocular hypotony :

Decreased IOP are typically found in patients with iridocyclitis .

Chronic uveitis affects secretory ciliary epithelium of ciliary body and

prevents its function and hence hypotony. Abnormalities in the

autonomic innervation also contributes to ocular hypotony.

Glaucoma :

Glaucoma is often unrecognized and untreated complication of

leprosy. Secondary open glaucoma with history of chronic uveitis and

chronic angle glaucoma after intra ocular inflammation are most

prominent types . POAG and acute angle closure glaucoma caused by

iris bombe also occur.

Cataract :

Primary and secondary cataract formation is responsible for

nearly half of blindness in leprosy. A possible cause of cataract

formation in leprosy is the reaction of M.leprae with dopa produces

high local concentration of quinones which are cataractogenic.

Direct invasion of lens by M.leprae have never been

demonstrated. Cataract can occur secondary to anterior segment

damage particularly iridocyclitis. Cataract is the most common cause of

blindness in leprosy and the social stigmata of the disease often exclude

patients from receiving surgery.

GENETICS

The following genes have been associated with leprosy. Hence,

susceptibility to leprosy may be atleast partially inheritable.

Susceptible loci on chromosome band 10p 13 and choromosome 6.

Polymorphisms in the gene promotor regions of TNF

( mutibacillary leprosy) and interleukin (IL-10)

HLA – HLA-DR2 and HLA –DR3 (tuberculoid disease) as well as

HLA- DQ1 (lepromatous leprosy)

TLR2 mutation in lepromatous leprosy

Polymorphisms in NRAMP1 gene in multibacillary disease in

African patients.

Genetic variants in the shared promotor region of PARK2 and

PACRG genes.

Taq1 polymorphism (tt genotype) at exon 9 of the vitamin D

receptor gene.

IMMUNOPATHOLOGY OF LEPROSY

Host response :

The varied and protracted manifestations of leprosy arise from

immunological response of the host against the virtually non-toxic M.

leprae. Glycolipids are the important surface antigens of mycobacteria .

Phenolic glycolipid I is unique to mycobacterium leprae. It has immuno

dominant trisaccharide segment and serves as a valuable chemical marker

for M.leprae infected tissues. Recent studies suggest HLA DR2 association

with tuberculoid leprosy.

Humoral immunity :

Humoral response in leprosy is not impaired, as patients usually have

raised levels of serum immunoglobulin. Peripheral blood- B cells, the

producer of antibodies against M.leprae have been demonstrated in

lepromatous leprosy. They have been found in the Ig G and Ig M classes.

The cell wall of M.Leprae protects it against these specific circulating

antibodies. Antibodies are harmful when they react with M.Leprae antigen

in the tissues, during type II reactions with the deposition of

immunoglobulin and complement in damaged tissues. Complement is

raised in patients having lepra reaction. Seropositivity proceeds in all types

of leprosy, particularly in LL patients who have very high antibody levels

at the time of diagnosis. This is used in the identification of individuals

progressing towards lepromatous form.

Cell mediated immunity :

Cellular immunity is normally responsible for limited bacterial

multiplication and is therefore essential for protective immunity and

resistance against leprosy. In tuberculoid leprosy cell mediated immunity

is strong and humoral response is weak, whereas the reverse is true in

lepromatous leprosy.

In lepromatous leprosy there is profound and specific deficiency of cell

mediated immunity to M.leprae which persists even after prolonged

chemotherapy. It suggests that it may be responsible for high risk of

relapse in these patients. M.Leprae is present in T- lymphocytes of LL

patients. There is insufficient production of IL-2 which results in failure of

proliferative T-cell lymphocyte response and macrophage activation upon

exposure to M.leprae.

Several theories are there for the development of leprosy. One

theory propose that leprosy patients has hereditary cellular

immunodeficiency that cause them to be unable to count an effective

resistance. The other theory suggests that in early stage, a few replicatory

organisms gain access to peripheral nerves where they are hidden from

immune surveillance system. Later as they multiply immune tolerance

develops producing a cellular immunodeficiency state.

Aetiological factors to immunological response in leprosy :

Though, it is accepted that the outcome of M.leprae infection depends

upon the host immune response. The reason for this diminished cell

mediated immunity is not exactly known. Various possibilities suggested

are :

Genetic constitution:

I. A possible association between leprosy and HLA haplotype has

been suggested by several workers but evidences are not conclusive.

II. Primary fault on T-cells there by rendering them unable to stimulate

macrophages.

III. Primary fault in macrophages thus making them unresponsive to T

cell stimulation.

IV. Suppressor cell activity – According to this hypothesis , there exists

a sub population of T-cells (suppressor cells ) which decrease the

immune response, but several contradictory observations have been

made by others.

V. Abnormal antigen presentation :

For a normal and effective cell mediated immunity to occur

against Mycobacterium leprae-leakage of bacillary antigens should

occur to the regional lymph nodes rather than to central lymphoid

component (spleen , thymus, bone marrow ) which results in a

humoral response and a suppressed cellular response . In leprosy

there is a continuous leakage of bacilli into circulation from the

affected nerves as they do not have true lymphatics , thus eliciting a

stronger humoral than a cellular response.

Immunopathology of uveitis :

Uveal involvement is more common in patients with disease of longer

duration and in patients on irregular treatment especially those belonging

to the lepromatous type. Anti-prostaglandin -1 and anti-LAM-B antibodies

were significantly higher in patients with ongoing uveitis but who were

skin smear negative. Thus insufficient chemotherapy and thereby

incomplete elimination of bacilli are the risk factors for occurrence of

uveitis in the quiescent stage of the disease. The role of immunogenetic

factors in the pathogenesis of uveitis in leprosy has also been extensively

studied and it has been suggested that there is an association between

HLA-DR2 antigen and susceptibility to uveitis in these patients.

Reactions in leprosy

The chronic benign course of leprosy at times , interrupted by

acute episode reactions which may cause irreversible damage if left

untreated.

History :

Though Danielsson et all and Hansen et all described a peculiar

eruption in lepromatous leprosy resembling Erythema nodosum, clinically

it was Muruta in 1912 who first named the condition Erythema nodosum

leprosum based on clinical and histopathological features. But ENL was

not clearly separated from other reactional states of leprosy until 1950’ s

when Cochrane put forward classification. Real breakthrough was made by

Ridely based on his observation on the histology of these lesions.

Classification (Jollife)

1. Type 1- Leprae reaction comprising of upgrading and downgrading

reactions.

2. Type 2 – Erythema nodosum leprosum.

Incidence :

Though it is difficult to determine the incidence of lepra reaction,

most authors agree that it’s occurrence has decreased since the advent of

the sulfones. A high incidence of about 40%-50% of all forms of lepra

reactions have been reported.

Clinical features :

Reactional states occur in about one third of patients and are due to

acute inflammation of the disease. A lepra reaction should be considered as

a medical emergency requiring immediate care. These states can result in

permanent neurological sequelae resulting in disability and deformity.

Patients at highest risk are those with multibacillary leprosy and / or pre-

existing nerve impairment.

I. Lepra reactions type I (reversal) reactions usually affect

patients with borderline disease. Reversal reactions shift toward the

tuberculoid pole after start of therapy and they are type IV cell mediated

allergic hypersensitives. Puberty, pregnancy, child birth can also

precipitate type I reactions. These reactions usually result in skin erythema,

with edema and tenderness of peripheral nerves. The peak time for type I

reaction is during the first 2 months of therapy up to 12 months.

Type II reaction / ENL :

Occur in 10% of patients with Borderline leprosy and in 20%

patients with Lepromatous leprosy. These are type III hypersensitivity

reactions with a systemic inflammatory response to immune complex

deposition. The most common presenting symptoms are crops of painful

erythematous nodules of the skin and subcutaneous tissue. Bullae, ulcers,

necrosis can occur. The reaction usually manifests after few years of

therapy. Although a single acute episode is possible, relapses occur

immediately or over several years. Associated fever, malaise, iridocylitis,

dactylitis, orchitis and proteinuria may be present.

Lucio phenomenon is an unusual type II reaction. It is common in

Mexico and Central America and is characterized by cutaneous

heamorrhagic infarcts in patients with diffuse lepromatous leprosy.

Ocular complications during lepra reaction :

The type I and type II reactions encountered during the course of the

disease cause ocular involvement within days. Type I lepra reactions

usually cause involvement of ophthalmic division of the trigeminal

nerve and zygomatic and temporal branches of the facial nerves.

Lagophthalmos often develops as a result of type I reaction, especially

when associated with an erythematous facial skin lesion. Type II

reaction usually cause acute iridocyclitis .Type II reactions may

develop in multibacillary patients with long standing untreated disease,

but up to 50% patients develop ENL within first year of anti-leprosy

treatment. Borderline lepromatous and lepromatous leprosy are in

particular risk of acute iridocyclitis and episcleritis during treatment

and needs yearly follow up.

Diagnosis

A diagnosis of leprosy can be arrived in majority by a proper

clinical examination alone, which involves a detailed history as well. This

procedure is called case taking which comprises of

1) Interrogation :

- Bio data of patients

- History of contact with other leprosy patients

- Previous treatment history

- Presenting compliant

2)Clinical Examination :

- A thorough inspection of the body for evidence of leprosy

- Palpation for thickened nerves

3) Laboratory diagnosis :

Tissue smear testing / slit skin smears:

An incision is made in the skin and scalpel blade is used to obtain

fluid from the lesion. The fluid is then placed on the glass slide and stained

by using Zheil-Neelson acid fast method or Fite method to look for the

organisms. The bacterial index is then determined as the number of

organisms per 100 bacilli. Skin smears have high specificity but low

sensitivity because 70% of all patients with leprosy have negative smears.

It detects most infectious patients.

4. Skin biopsy :

Skin biopsy samples are stained with hematoxylin-eosin and Fite-

Faraco. It is the primary basis for laboratory diagnosis and categorization.

The presence of an inflamed nerve in a skin biopsy is considered as

standard criteria for diagnosis. A full thickness skin biopsy sample should

be taken from an advancing border of an active lesion and should include

epidermis and dermis. Skin smears that demonstrate acid fast bacilli

strongly suggest the diagnosis, but the bacilli may not be demonstrable in

tuberculoid (paucibacillary) form of the disease. The skin biopsy sample

should be examined for morphological features and presence of acid-fast

bacilli. Biopsy is useful for determining the morphological index (MPI)

which is used in evaluation and treatment of patients. The MI is the

number of viable bacilli per 100 bacilli in leprous tissue.

5) Nerve Biopsy :

A nerve biopsy can be useful in ruling out diseases such as

hereditary neuropathies or polyarteritis nodosa. They also help to identify

abnormalities in sub-clinical leprosy. It is the only way to diagnose

definitively in patients with completely neuropathic forms of leprosy.

6) Foot pad culture :

Mouse foot pad inoculation is most sensitive in detecting

Mycobaterium leprae than slit skin smears.

It is used for

1. Detection of drug resistance

2. Evaluation of potency of antileprotic drugs

3. Detection of viability of bacilli during treatment

The disadvantage of this method is that it is time consuming and

requires 6-9 months before the results are obtained.

7) Histamine testing :

This test is used to diagnose post-ganglionic nerve injury. Histamine

diphosphate is dropped on normal skin and affected skin. A pinprick is

made through each site. The site forms a wheal on normal skin but not

where nerve damage is present.

8) Methacholine sweat testing :

A intra-dermal injection of methacoline demonstrates the absence of

sweating in leprous lesions. This testing is useful in dark skinned patients

in whom the flare with histamine test cannot be seen.

Immunologic tests :

1. Lepromin testing :

This test indicates host resistance to M.leprae by assessing the

patients ability to mount an granulomatous response against a skin

injection of killed M. leprae. It results do not confirm the diagnosis, but

they are useful in determining the type of leprosy. A positive testing

(>5mm) indicates cell-mediated immunity, which is observed in

tuberculoid leprosy. A negative finding suggests a lack of resistance to

disease and is observed in lepromatous leprosy. A negative test result also

indicates a poor prognosis.

Procedure:

To perform this test, bacillary suspension is injected into forearm. An

assessment of the reaction at 48 hours is called Fernandez reaction and

indicates delayed hypersensitivity to antigens of M.leprae or

Mycobacterium that cross react with M.leprae. When the reaction is read

at 3-4 weeks it is called Mitsuda reaction and indicates that immune

system is capable of mounting an efficient cell-mediated response.

2.PGL -1 :

This is a specific serological test. It is based on antibodies to phenolic

glycolipid-1 – (PGL-1). This test has a sensitivity of 95 % for the

detection of lepromatous disease, but only 30% for tuberculoid disease.

3. Lymphocyte Migration Inhibition test (LMIT) :

As determined by a lymphocyte transformation and LMIT, cell-

mediated immunity is absent in lepromatous form of the disease but

present in tuberculoid form of the disease.

Serology and polymerase chain reaction :

Although these tests are useful in detecting multibacillary

disease, they are not widely used because they fail to detect early or milder

forms of the disease reliably.

Serology can be used to detect antibodies to M.leprae specific

PGL-1. This test is useful primarily in patients with untreated LL, as 90%

of patients have antibodies. However antibodies are present only in 40-

50% patients with paucibacillary disease.

PCR analysis can be used to detect and identify M.leprae. The

technique is used most often when acid fast bacilli are detected but

clinical/ histopathological features are atypical. It is not useful when AFB

is not detected by light microscopy. M.leprae DNA can be detected by

using RT-PCR in ocular tissues,when acid fast bacilli are seen in

histopathological section and when the diagnosis of leprosy is

inconclusive. RT-PCR for M.leprae DNA could be used as a rapid

confirmatory test to identify the presence of M.leprae and therefore the

diagnosis of leprosy. The development of one –step reverse transcriptase

PCR (RT-PCR) may be most sensitive in detecting bacilli in slit smears

and skin biopsy specimens. This RNA based assay is also effective in

monitoring bacteria clearance during therapy.

Imaging studies :

Radiographs :

Plain radiographs are useful to detect and monitor leprosy induced

bone changes. Resorption, fragmentation and mal-aligned fractures are

common signs of leprosy induced bone changes. Medullary sclerosis or

wavy diaphyseal borders indicate diaphyseal whittling.

Histologic findings :

In TT form well developed epitheloid granulomas are

observed in the papillary dermis, often around neovascular structures. The

granulomas are surrounded by lymphocytes which extend into epidermis.

Langerhans giant cells are common. Dermal nerves are destroyed / swollen

because of the granulomas. Acid fast bacilli are not observed. S-100 is

useful in identifying nerve fragmentation and differentiating it .

In the LL form, a diffuse infiltrate of foamy macrophages is

present in the dermis below the sub-epidermal grenz zone. An enormous

number of AFB develop within foamy macrophages, singly or in clumps

called globi. Lymphocytes are scant and giant cells are typically absent.

Numerous bacilli invade the nerves but these are fairly well preserved with

little infiltrate. Nodular / dermatofibroma-like lesions in LL, referred to as

histoid leprosy result in fascicular arrangement of spindle cells in the

dermis admixed with foamy macrophages that contain numerous bacilli.

Histopathology of ocular tissues discloses far more silent chronic

iridocyclitis in leprosy patients than are diagnosed clinically. AFB can

persist in the iris tissue even after completion of MDT. Smooth muscle

disruption and destruction causes miotic pupil in leprosy and has been

conclusively demonstrated histopathologically.

MANAGEMENT

The management of leprosy includes pharmacothreapy and

physical, social, psychological rehabilitation. The goals of

pharmacotherapy are to stop the infection, reduce morbidity, prevent

complications and eradicate the disease. Since 1981 MDT has been

advocated by World Health Organisation (WHO) and US.

MDT prevents dapsone resistance, reduces relapses, reactions

and disabilities. The length of treatment ranges from 6 months to 2years.

Patients are considered non-infectious within 1-2 weeks of treatment

(usually after first dose )

Current WHO recommendations for treatment of leprosy are as follows :

Paucibacillary disease :

Dapsone 100mg/day plus rifampicin 600mg once a month for 6

months .

Multibacillary disease :

Dapsone 100mg/day plus rifampicin 600mg once a month plus

clofazimine 300mg once a month and 50 mg /day for 1year.

MDT Regimens :

Treatment for lepra Reaction :

Reaction Prednisolone Clofazamine ThaliodomideReversal

reaction

(Type1)

ENL

(Type 2)

Up to 1mg/kg/day then

gradually reduced

Up to 1mg/kg/day then

gradually reduced

Upto 300mg Upto 400mg

Combination therapy is recommended in ENL

Thalidomide should be avoided in women of child bearing age

- Corticosteroid treatment is aimed at controlling acute inflammation,

relieving pain and reverses nerve and eye damage. With treatment,

approximately 60-70% of patients nerve function is recovered. If neuritis is

absent, non-steroidal anti-inflammatory drugs may be useful.

Erythema nodosum leprosum :

The use of clofazamine in MDT substantially reduces the incidence of

ENL to 5% clofazamine has also been used to treat ENL.

Thalidomide is effective in ENL except in case of neuritis / Iritis in

which case, corticosteroids should be used. Other treatment therapies

reported to be effective include colchicine, pentoxiphylline, cyclosporine

A, intravenous immunoglobulin (IVIG) and infliximab. Lowering the dose

of dapsone may decrease the severity of bullae and ulcers

In lucio phenomenon, thalidomide is ineffective. Azathioprine /

Cyclophosphamide with corticosteroids with or without plasmapheresis

has been used.

Prevention and treatment of Deformites :

Potential deformities can be prevented by educating patients about how

to minimize existing nerve damage and by treating any sequlae of this

damage. Close follow up is important to ensure patient compliance.

Emergency surgery may be necessary if a patient with profound

inflammation presents with nerve abscess / loss of nerve function

secondary to compression.Prompt recognition and surgical drainage of the

abscess can often restore nerve function.

Reconstructive surgery can be used to repair nasal collapse in

LL.Other surgery may be needed to improve function or for cosmesis,

Contractures can be surgically repaired .

Management of ocular complications of leprosy :

Madarosis Island of neurovascular pedicle graft from the scalpUpper lid ectropion Blepharoplasty with correction of lid inversion Lower lid ectropion Tarsal strip procedureTrichiasis Cryoablation of abnormal lashesDacryocystitis

Dacryoadenitis

Systemic antibiotics with dacryorhinostomy /

dacryocystectomy.

Systemic antibiotics with anti-inflammatory drugsLagophthalmos with

exposure

Acute : Immediate treatment with prednisolone,

thalidomide or clofazamine.

Chronic : Eyelid exercise using maximum effort with

artificial lubricants .

Tarsorraphy / temporalis muscle transfer. Limbal lepromas Systemic antileprotic therapyEpiscleritis and

scleritis

Topical / systemic anti-inflammatory agents

Corneal hypesthesia Patient education about regular surveillance

Eye protection with sun glasses & lubricantsAcute iridocyclitis

Chr

onic iridocyclitis

Treatment of systemic ENL if present

Topical steroids & mydriatics / cycloplegic agents , IOP

monitoring Topical mydriatics

Topical steroids if anterior chamber reaction is severeCataract Cataract extraction with or without implantation of IOL

depending on the presence or absence of uveitisGlaucoma Standard management of open angle glaucoma ,angle

closure or complicated glaucoma with synechiae

Drug and side effects :

Rifampicin (RFP) :

The drug is administered in a single monthly dose, a protocol

for which no significant toxic effect has been reported. Exceptionally

bactericidal against M.leprae and single dose of 600mg of RFP is capable

of killing 99.9% or more of viable organisms. However the rate of killing

is not proportionately enhanced by subsequent doses. It has been suggested

that RFP may exert a delayed antibiotic effect for several days during

which organisms multiplication is inhibited. The high bactericidal activity

of RFP made feasible the application of the single monthly dose, which is

cost-effective for leprosy control programs.

Side effects :

Red colouration of urine and other side effects include skin rash ,

peripheral neuropathy, hemolytic anemia, flu-like syndrome.

Di-amino diphenyl sulfonoe (DDS, dapsone ) :

Until widespread resistant strains to drug were reported, dapsone

which is bacteriostatic / weakly bactericidal against M.leprae was for years

the mainstay treatment regimen for leprosy. Subsequently its use in

combination with other drugs has become essential to slow or prevent the

development of resistance. The drug has demonstrated an acceptable level

of safety in the dosage used in MDT.

Side effects :

Besides occasional cutaneous eruptions, side effects that necessitate

discontinuation are rare. Patients known to be allergic to any of sulfa drugs

should be spared dapsone. Anemia, hemolytic and methemoglobinemia

may develop but are more significant in patients deficient for glucose-6-

phosphodihydrogenase (G6PD)

Clofazimine (CLF) :

CLF which preferentially binds to mycobacterial DNA inhibits both

mycobacterial growth and exerts a slow bactericidal effect on M.leprae.

Because of its anti-inflammatory properties it is suggested for the erythema

nodosum leprosum reactions by mechanisms still poorly understood.

Most active when administered daily , dosage used for MDT is well

tolerated and has not shown significant toxicity. Because CLF is a

repository drug, stored in the body after administration and slowly

excreted. It is given as a loading dose of 300mg once a month to ensure

that the optimal amount of CLF is maintained in the body tissue even if

patients occasionally miss the daily dose.

Side effects :

Brownish black discolouration and dryness of skin. These usually

disappear within few months of treatment suspension. Other side effects

include abdominal pain, diarrhea, phototoxicity.

Ofloxacin (oflx):

OFLX a synthetic fluoroquinolone acts as a specific inhibitor of

bacterial DNA gyrase and has shown efficiency in the treatment of

M.leprae. Chromosomal resistance of negligible clinical relevance has

been reported .

Minocycline (MINO) :

MINO is a semisynthetic tetracycline in susceptible organisms and

induces bateriostasis by inhibiting protein synthesis.

However from the curative and cost-effectiveness points of view ,the

WHO recommended MDT remains to date the best combination regimen

of the worldwide leprosy control programme.

Laboratory monitoring for drugs used to treat leprosy includes :

Drug Laboratory studies FrequencyInitial studies for

all drugsDDS

RFP

CLF

Thalidomide

CBC, platelets

G6PD,CBC

CBC,platelets,hemoglobulin

No recommended lab studies

CBC

Baseline

Every 6 months

Every 3 months

Every 3 months

Every 2 months

Prevention

The basic factors in the prevention of leprosy in endemic regions are:

1. Case finding and prompt treatment of all cases found, with

multidrug therapy.

2. Keeping close contacts of patients under surveillance.

3. Vaccination of all young children, especially those born in leprous

families and to lepromin negative contacts of index cases with BCG

vaccine.

4. Improvement in socioeconomic condition.

5. Health education and publicity about leprosy and about early

presentation for diagnosis and cure by multidrug therapy

Attempts to develop a vaccine against M.leprae are being

made that may induce immunity in non-infectious patients and a high

level of immunity in leprosy patients. This is based on the theory that

cross immunity exists between TB and leprosy. Thus BCG is a cheap

and safe substitute until a specific anti-leprosy vaccine is discovered.

But the extent to which elimination and eradication of leprosy will

depend mainly on improvement in socioeconomic conditions as Latapi

the renowned Mexican Leprologist said` Leprosy cannot be completely

rooted out with physicians, control officers, leprosaria and propaganda’.

It will disappear when the economic and cultural factors change,

because leprosy is the thermometer of civilization.

The strategy for leprosy elimination :

The following actions are part of the ongoing leprosy elimination

campaign :

1) Ensuring accessible and uninterrupted MDT services are

available to all patients through flexible and patient friendly drug

delivery systems.

2) Ensuring the sustainability of MDT services by integrating

leprosy services into general health services. Building the ability

of general health workers to treat leprosy.

3) Encouraging self reporting and early treatment by promoting

community awareness and changing the image of leprosy.

4) Monitoring the performance of MDT services the quality of

patients care and the progress being made towards elimination

through national disease surveillance systems.

AIMS AND OBJECTIVES

1. To analyse the ocular manifestations of leprosy in a

hospital population.

2. To analyse the incidence of ocular complications and

visual outcome.

MATERIALS AND METHODS

A prospective and descriptive study on ocular manifestations of

leprosy and its management was conducted in Government Rajaji Hospital

– Department of ophthalmology, Madurai. This study was conducted from

January 2007 to Dec-2007, during which 46 patients with ocular

manifestations were analyzed. In this study all the patients with systemic

leprosy who presented to the department of Dermatology outpatient were

referred to the department of Ophthalmology and screened for ocular

manifestations.

Inclusion criteria :

All leprosy patients who attended department of ophthalmology, GRH

in the period from Jan-2007 to Dec -2007.

Exclusion criteria :

Patients with co-morbid condition like HIV were excluded from the

study.

Clinical evaluation :

In all these patients demographic data like age, sex, place of

residence were documented. A detailed history regarding systemic

symptoms of leprosy like defective vision, redness, pain, loss of eyelids

were documented.

An elaborate treatment history regarding

(i) Year of onset of skin lesions and the latency period if any,

of the start of systemic treatment.

(ii) Duration and regularity of treatment.

(iii) Type of treatment – monodrug / multidrug were elicited.

The patients were examined for ocular manifestations and systemic

manifestations of leprosy.

Ocular examination included :

(i) Best corrected visual acuity.

(ii) Slit lamp examination for the type of keratic precipitates, anterior

chamber reactions, iris features, posterior synechiae, lens

changes and scleritis.

(iii) Dilated fundus examination by indirect ophthalmoscopy, +90D

slitlamp biomicroscopy.

(iv) SLE : To look for episcleritis, scleritis, keratitis, exposure

keratopathy, uveitis and cataract.

(v) Corneal sensation : Tested by asking the patient to look up and

applying tail end of wisp of cotton on the cornea 2mm from the

limbus at the 6’ clock position and categorizing the sensation as

normal if the patient responded by retracting the head (or)

closing the eyelids. It is impaired if the patient didn’t.

(vi) Detailed external ocular examination done with the help of torch

light to look for madarosis, lagophthalmos, lid nodules.

Systemic evaluation was done to assess

1) Skin lesion

2) Neuropathies

3) Deformites

Based on this patients were grouped according to WHO classification

of visual impairment and blindness.

Grading Category of visual

Impairment

Best corrected visual acuity in the better eye

0 Normal 6/6 to 6/18 i.e – can see 6/18 or better1 Visual

Impairment<6/18 to 6/60 i.e – cannot see 6/18 can see 6/60

2 Severe Visual Impairment

<6/60 to 3/60 i.e – cannot see 6/60 can see 3/60

3 Blind <3/60 to 1/60 i.e – cannot see 3/60 can see 1/604 Blind <1/60 to only light perception i.e –cannot see 1/60

can see light5 Blind No light perception i.e – cannot see light6 Undetermined or

unspecified

Intra ocular pressure was recorded in all patients above 40 years by

schiotz tonometer. Gonioscopy was done with Goldmann goniolens in

suspected cases of narrow angles and graded according to shaffers

classification. Fields were done in Humphery perimeter in selected cases.

After establishing the diagnosis, appropriate treatment was started.

Patients with acute granulomatous or non- granulomatous uveitis were

treated with topical steroids – 1% prednisolone acetate frequency being

determined by severity of iritis at the time of presentation, cycloplegics –

homatropine eyedrops 2 times/day and oral non-steroidal anti-

inflammatory agents – tablet Ibubrofen 500 mg twice a day. Patients with

episcleritis and scleritis were treated with topical steroids like %

prednisolone acetate. Patients with severe or recurrent intra- ocular

inflammation suspected to be due to active leprosy were started on anti-

leprosy treatment and systemic steroids after consulting the dermatologists.

Anti- glaucoma medications were started in patients with raised intra-

ocular pressure. Secondary angle closure glaucoma patients with cataract

underwent cataract extraction with intraocular lens implantation after

ocular inflammation is controlled with topical steroids or systemic steroids.

Lateral tarsorraphy was done in patients with lagophthalmos with exposure

keratopathy. Patients were followed over subsequent visits. During each

visit BCVA, ocular status and skin lesion were assessed.

At the end of the study period, all the data were analyzed. The pattern of

ocular involvement in these patients were analyzed. The correlation

between anti-leprosy treatment and ocular involvement were analyzed.

The visual outcome of the treatment were analyzed for those patients who

had atleast three follow up’s during the study period.

PROFORMA

Name : Age : Date :

Sex : 1: Male, 2 : Female Occupation :

Address :

History (Present – 1, Absent – 2)

Skin Lesion Weakness or anaesthesia of limbsNasal symptoms Edema of legs

Year of onset of skin lesion ____ year of diagnosis year of treatment

Type of Leprosy

1 – TT 2 – BT 3 – BB 4 - BL 5 - LL

Ocular symptoms of Leprosy

1. Pain 2. Redness 3. DV 4. Loss of eyebrows 5. Inability to close lids

Occurrence of ocular symptoms

1. During treatment 2. After treatment

Lepra Reaction

1 – Present , 2 – Absent

Type – 1 Erythema of existing lesions Nerve palsy

Edema of existing lesion

Type – II Fever Epistaxis Edema of legs

Epididymoorchitis Malaise Joint pain

New skin lesions Dactylitis Others

Precipitating factor

1. Pregnancy 2. Vaccination 3. Trauma 4. Recent ALT 5. Nil

Ocular symptoms of Lepra reaction

A) 1. Pain 2. Redness 3. Photophobia 4. DV 5. Floaters

B) No.of episodes of Lepra reaction

C) Time of occurrence

1. Before treatment 2. During 3. After treatment

Treatment given for ocular symptoms of lepra reaction

1. Topical steroids 2. Systemic steroids 3. ALT 4. Antiglacoma

drug

5. NSAID 6. Thalidomide 7. Others

Dosage : ____________

Duration : _____________

Treatment History for leprosy

1. Multidrug 2. Monodrug 3. Mono to multi drug 4. Details not

known

5. Treatment not taken

A) Drugs : Dapsone Rifampicin Clofazamine Steroids Others

Dosage : ____________

Duration : _____________

B) Total duration of treatment

C) Treatment Status : 1. Completed treatment 2. Undergoing

treatment

D) Compliance : 1. Regular 2. Irregular

EXAMINATION : Systemic :

Skin : Hypopigmented patches 1. 0 2. < 6 3. > 6

Neuropathy : 1. Trigeminal 2. Facial 3. Ulnar 4. Radial 5. Median

6. Greater auricular 7. Deep peroneal 8. Posterior tibial

9. No neuropathy

1. Right 2. Left 3. Both

Deformities of Extremities Nasal deformities Present – 1, Absent - 2

Ocular Examination :

Laterality : 1. Unilateral 2. Bilateral 3. One eyed

Manifestations R E L E Manifestations R E L EMadarosis Iris atrophyLagophthalmos Iris nodulesLid nodules CataractEpiscleritis Lepra pearlsScleritis Others

1. Corneal ulcer2. Adherent leucoma3. Phthisis bulbi4. Dacryocystitis

Corneal sensation BCVAIridocyclitis IOPGranulomatous Fundus

1. Normal2. Glaucomatous3. Others4. Hazy view

Non granulomatousAcute / chronic

Surgery :

1. Unilateral 2. Bilateral 3. Not done 4. combined

surgery

Type of surgery : ____________________ 1. R E 2. L E

Post op. Complications :

1. Present 2. Absent

Post of vision : ____________________________

Follow up I II III IV VA BCVA (RE)

BCVA (LE)B Skin lesionsC Ocular lesions (RE)

(LE) Improved - 1 Static - 2 Worsened - 3

Treatment :

Investigations :

RESULTS

In this study, 46 patients with ocular leprosy were analysed. Among

46 patients, 4 had lepra reaction. Patients demographic characteristics are

shown in table 1 and 2. Most of the patients were in 6th – 7th decade of life.

Majority of patients (80.43%) were males.

Type of leprosy is shown in table 3. Majority of patients (80.43%)

had lepromatous leprosy. Among lepromatous leprosy, lepra reactions

were noted in 4 patients. The time of occurrence of ocular manifestations

in leprosy is shown in table 4. Ocular manifestations were predominantly

seen (91.3%) after treatment.

The details of anti-leprosy treatment are shown in table 5and 6.

Among 46 patients 44 of them had already taken treatment (94.4%). In the

remaining 2 patients type of treatment was not known in 1 patient and 1

patient didn’t receive treatment. The predominant regimen were multidrug

therapy (54.34%) and monotherapy (33.3%).

67.39% of patients had successfully completed their treatment with

good compliance. Systemic features such as skin lesions, neuropathy are

shown in the table 8 and 9 respectively. Among them only 17.39% had

skin lesions, the remaining 82.61% had no skin lesions. Peripheral

neuropathy was observed in 31.8% of patients. Ulnar nerve was the most

common neuropathy followed by common peroneal nerve and greater

auricular nerve in both the subgroup of patients. Data obtained from

(ocular evaluation) are discussed below. Table 10 shows that majority

(72.72%) of patients had bilateral involvement. 12 patients had unilateral

involvement and 6 were monocular. Table 11 shows that madarosis

(80.30%) was the most common adenexal ocular manifestation in both the

sub groups.

Table 12 and 13 shows the pattern of ocular involvement in these

patients. Chronic granulomatous uveitis was seen in 36.52% of eyes.

Decreased corneal sensation was observed in 37.1 % of patients . Corneal

leucoma was observed in (6.12% ) and corneal ulcer was observed in

(2.04%) of patients . Episcleritis (4.54%) and scleritis (4.54%) were

reported. 45 eyes out of 66 eyes showed iris atrophy and iris nodules were

observed in 1 patient. Lepra pearls were seen in 1 patient.

Table 14 shows the analysis of type of cataract. 30 eyes had cataract

of which 17 were complicated cataract, 13 were senile type. Findings of

posterior segment are showed majority of patients (84.84%) had normal

fundus. Glaucomatous disc was observed in 3.03% patients. Fundus view

was hazy and could not be assessed due to cataract in 10.68% patients.

Intraocular pressure was recorded in all patients. Majority had normal

IOP. Ocular hypotony was seen in 6.06% of patients. Glaucoma was seen

in 3.03% of patients. Antiglaucoma medications were required in 11.11%

of patients.

The details of cataract surgeries were shown in table. 20

out of 66 eyes underwent cataract surgery. One patient underwent

combined procedure (cataract surgery with trabeculectomy). 95% had

good visual outcome.

WHO grading of visual impairment of the patients were shown in

table. 10.86% had severe visual impairment. 10.88% of patients met with

blindness criteria.

Potentially sight threatening lesions (PSTL) are those that cause

visual impairment and blindness. PSTL include lagopthalmos, corneal

hyposensitivity, keratitis, iris involvement and post operative

inflammation.

Lagophthalmos (4 patients) were examined for adequate Bells

phenomenon and corneal sensation. Patients with lagophthalmos with

indadequate Bells phenomenon were treated with temporary lateral

tarsorraphy (8 patients). They were observed for exposure keratitis,

secondary bacterial keratitis during their follow up.

Patients having neurotrophic and neuroparalytic keratitis (7patients)

were observed for exposure keratitis and secondary bacterial keratitis. Two

patients were not compliant with their follow up and developed severe

secondary bacterial keratitis and perforation. Our best treatment prevented

them developing blindness and gained vision 4/60.

Cataract surgery in inflamed eyes is a challenge to even an experienced

ophthalmic surgeon. Preoperatively all patients were evaluated in Slit

lamp to rule out active inflammation. All patients were preoperatively

treated with hourly steroid eye drops.

Due to our meticulous surgery and minimum tissue handling during

surgery we landed up with few post operative complications. Patients

were given intense steroid therapy depending upon the severity of

inflammation. Inspite of our best efforts, 2 patients developed severe post

op inflammation leading to deterioration of vision upto 6/60.

Remaining 52.17 % patients had normal visual acuity.

Majority of patients (66.67%) of patients were treated with steroids. Anti-

leprosy treatment was restarted in 19.44% of patients. One patient with

history of lepra reaction were treated with thalidomide.

The follow up and treatment response of these patients are

analysed. 19 patients had come for more than 3 follow ups. Ocular

inflammation had improved in 75% patients, static in 8.33%. In these

patients with history of lepra reaction only one patient had come for

regular follow up and there was good improvement in ocular condition.

The skin lesion was static in all patients.

Table -1 Age distribution

Age group No.of leprosy patients 30 - 39 240 - 49 750 - 59 1860 - 69 1670 - 79 3Total 46

Most common age group 6th – 7th decade

Table - 2 Gender

Gender No .of leprosy patients PercentageMale 37 80.5

Female 9 19.5Total 46 100

Table – 3 Type of leprosy

Type of leprosy No. of leprosy patients PercentageTuberculoid 9 19.5Lepromatous 37 80.5Total 46 100

Table -4 time of occurrence of ocular symptoms of leprosy

Time of occurrence of

ocular symptoms

No.of leprosy patients Percentage

During treatment 4 8.7After treatment 42 91.3Total 46 100

Table – 5 Time of occurrence of lepra reaction

Treatment status No .of patients with

lepra reactionBefore start of treatment 0While on treatment 3After completing treatment 1Total 4

Table - 6 Treatment History

Type of medical treatment No .of leprosy patientsMultidrug 25Monodrug 13Monodrug to Multidrug 6Details not known 1Treatment not taken 1Total 46

Table - 7 Compliance

Compliance No.of leprosy patientsRegular 30Irregular 14Treatment details not known 2Total 46

Table - 8 Skin lesions

Hypopigmented patches No.of leprosy patientsNil 38<6 7

>=6 1Total 46

Table -9 Neuropathy

Neuropathy No . of leprosy patientsTrigeminal 1Facial 4Ulnar 17Radial 0Median 0Greater auricular 5Common peroneal 8Posterior tibial 1Nil 26

Table -10 - Laterality

Laterality No .of eyesUnilateral 12Bilateral 48One eyed 6Total 66

Table - 11 Ocular Adenexal manifestations

Clinical signs No . of eyesMadarosis 53Lagophthalmos 14Lid nodules 0Chronic dacryocystitis 3

Table -12 Ocular manifestations

Clinical signs No .of eyesEpiscleritis 3Scleritis 3Decreased corneal sensation 24Acute granulomatous uveitis 16Chronic granulomatous uveitis 24Acute nongranulomatous uveitis 6Chronic nongranulomatous uveitis 4Adherent leucoma 4Corneal ulcer 2

Table -13 Cataract

Type of cataract No. of eyes PercentageComplicated cataract 17 25.5Senile cataract 13 20Nil 36 54.5Total 66 100

Table -14 Grading of visual impairment

Grade No .of eyes PercentageNormal 24 52Visual impairment 12 26Severe visual impairment 5 11Blind 5 11Total 46 100

Table -15 Immediate postoperative vision after cataract surgery

Best corrected visual acuity No .of eyes6/6 - 6/12 176/18 - 6/36 2

< 6/60 1Total 20

Table -16 Follow up

Number of follow up No .of leprosy patientsNil 15

1 - 2 123 - 5 19Total 46

Table -17 Treatment response for inflammation

Treatment response of

inflammation

No of leprosy patientOcular Systemic

Improved 16 0Static 4 16

Worsened 2 0Total 22 16

DISCUSSION

Leprosy is a disease which is still endemic in 120 developing

countries and also contributes to significant cause of blindness. Most of the

blindness is avoidable and could have been prevented by early diagnosis of

ocular leprosy, early systemic anti-leprosy treatment, timely treatment of

immune reactions and prompt treatment of ocular complications. Our study

results were consistent with this finding.

According to longitudinal study on ocular leprosy (Ethiopia, India

& Philippines) 2.8% are blind at the time of diagnosis and 11% had

potentially blinding complications. Our study results were consistent with

this findings.

The demographic profile of these 46 patients in this current study

is consistent with published reports. The age group of presentation in our

study was between 4th -8th decade majority being in their 6th -7th decade.

This is similar to previous reports. The sex incidence in our study revealed

a male:female ratio ( 4:1) which is comparable to other studies in

literature. The male preponderance is because males in general expose

themselves to greater risks of infection as a result of their life style. This

male preponderance is seen even in patients with a history of lepra

reaction, on the other hand women may not tend to seek medical help even

when it is required.

It is well known that persistence or recurrence of inflammation

can occur long after systemic infection was treated with ALT. Though

routine skin smear may be negative after completion of treatment, the

persistence of M.leprae in the fibrosed nerves may be responsible for

chronic uveitis seen in these patients. Espirito et al had reported an

incidence ranging from 5.3% to 63% of chronic iridocyclitis in patients

treated for leprosy.

Systemic evaluation revealed that majority had no skin lesions at

the time of presentation of ocular symptoms. The most common

neuropathy was ulnar nerve followed by deep peroneal nerve in both the

subgroup of patients. Deformities of the extremities and depressed nasal

bridge were found to be more common in lepromatous type.

In ocular evaluation madarosis was the most common ocular

adenexal manifestation seen in our study. These findings are consistent

with previous reports. Lagophthalmos was seen in 33.3% patients. In

patients with Lagophthalmos the Bells phenomenon was assessed. Patient

with adequate Bells phenomenon (4 patients) were treated with lubricants.

Patients with inadequate Bells phenomenon were treated with temporary

lateral tarsorraphy (8patients). The reports of other abnormalities of lid

like entropion and ectropion were very few. Among 46 patients 5 patients

had phthsis bulbi at presentation, the reason for phthisis was not evaluated.

The commonest form of uveitis in lepromatous leprosy is chronic

low grade insidious type of uveitis. In our study the commonest type of

uveitis is chronic low grade uveitis which is also consistent with this fact.

Iris atophy is a common finding in the chronic uveitis. Iris pearls

are chalky white particles in the superficial connective tissue of the

pupillary margin Mithal et al had reported an incidence of these findings

which are compared with our study. Iris atrophy was seen in 60 %.

Episcleritis and scleritis were seen in 4.54% of patients. None of

the patients with history of lepra reaction had scleritis or episcleritis.

Tajamul khan et al in his study found the incidence of episcleritis to be

around 1%.

Leprotic pearl were seen 1 patient and iris nodules were seen in 1

patient. According to a study Ebenezor et al it was found that iris atrophy

continues to develop in 3% of patients with MB leprosy every year after

they complete their 2 year course of MDT and is associated with age,

increasing loads of mycobacteria, subclinical inflammation, cataract and

corneal opacity.

CONCLUSION

In this prospective and descriptive study done in Government

Rajaji Hospital during January 2007 to December 2007, 46 patients

with ocular leprosy were analysed.

Among these 46 patients who presented with ocular leprosy, 4

patients had history of lepra reaction.

Cataract surgery alone was done in 19 patients. Combined

surgery was done in 1 patient. 95% of patients had good visual

outcome after cataract surgery.

Temporary lateral tarsorraphy was done in 8 patients of

lagophthalmos having inadequate Bells phenomenon.

Majority of these patients had developed ocular manifestations

despite completing anti-leprosy treatment with good compliance, thus

emphasizing the importance of monitoring patients even after

completing treatment.

Majority of patients treated for ocular inflammation had good

visual outcome.

BIBLIOGRAPHY

1. "Editorial: Blindness in leprosy" BR J OPHTHALMOL VOL: 65

(4) 1981 APR. P.221-222 Type: Editorial.

2. ACHARYA B P "Clinical observation on iridocyclitis in leprosy

patients" INDIAN J OPHTHALMOL VOL: 30 1982 MAR. P.65.

3. Acharya, B P "Ocular Involvement in Leprosy: a study in mining

areas of India" INDIAN J OPHTHALMOL VOL: 26 (2) 1978

JUL. P.21-24.

4. ALLEN James H "The pathology of ocular leprosy- II. Miliary

lepromas of the iris" AM. J. OPHTHALMOL VOL: 61 (5- PT.2)

1966 MAY P.987/47.

5. Balakrishnan, E "Survey of Ocular Complications in Lepromatous

Leprosy" INDIAN J OPHTHALMOL VOL: 14 (5) 1966 OCT.

P.214-216.

6. Betharia, S M; Bhaumik, S Evaluation of Different Surgical

Techniques in the Management of Paralytic Ectropion in Cases of

Leprosy" AFRO ASIAN J OPHTHALMOL VOL: 7 (4) 1989

MAR. P.121-124.

7. Brandt, F Zhou, H M; Shi, Z R; Rai, N; Thuladar, L; Pradhan, H

Histopathological Findings in the Iris of Dapsone Treated Leprosy

Patients" BR J OPHTHALMOL VOL: 74 (1) 1990 JAN. P.14-18.

8. Chaudhry, Imtiaz A Shansi, Farrukh A; Elzaridi, Elsanusi;

Awad,Abdulaziz; Al-Fraikh, Hamad; Al-Amry, Mohammed; Al-

Dhibi, Hassan; Riley, Fenwick C "Initial Diagnosis of Leprosy in

Patients Treated by an Ophthalmologist and Confirmation by

Conventional Analysis and Polymerase Chain Reaction"

OPHTHALMOLOGY VOL: 114 (10) 2007 OCT. P.1904-1911.

9. Courtright, Paul Lewallen, Susan; Tungpakorn, Narong; Cho,

Byeong-Hee; Lim, Young-Kyu; Lee, Hyun-Ji; Kim, Sung-Hwa

"Cataract in leprosy patients: cataract surgical coverage, barriers to

acceptance of surgery, and outcome of surgery in a population based

survey in Korea" BR J OPHTHALMOL VOL: 85 (6) 2001 JUN.

P.643-647

10.Daniel, E Ffytche, T J; Kempen, J H; Rao, P S S Sundar; Diener-

West, M; Courtright, P "Incidence of Ocular Complications in

Patients with Multibacillary Leprosy after Completion of a 2 Year

Course of Multidrug Therapy" BR J OPHTHALMOL VOL: 90 (8)

2006 AUG. P.949-954

11.Daniel, E Ffytche, T J; Rao, P S S Sundar; Kempen, J H; Diener-

West, M; Courtright, P "Incidence of Ocular Morbidity among

Multibacillary Leprosy Patients during a 2 Year Course of

Multidrug Therapy" BR J OPHTHALMOL VOL: 90 (5) 2006

MAY P.568-573

12.Daniel, E Koshy, S; Rao, G Sundar; Rao, P S S S "Ocular

Complications in Newly Diagnosed Borderline Lepromatous and

Lepromatous Leprosy Patients: baseline profile of the Indian cohort"

BR J OPHTHALMOL VOL: 86 (12) 2002 DEC. P.1336-1340

13.Daniel, Ebenezer Duraisamy, Muruganand; Ebenezer, Gigi J;

Shobhana, J; Job, Charles K "Elevated Free Tear Lactoferrin Levels

in Leprosy are Associated with Type 2 Reactions" INDIAN J

OPHTHALMOL VOL: 52 (1) 2004 MAR. P.51-56

14. Daniel, Ebenezer Rao, Sundar P S S; Ffytche, Timothy J;

Chacko, Shirley; Prasanth, Hannah Rajee; Courtright, Paul "Iris

Atrophy In Patients With Newly Diagnosed Multibacillary Leprosy:

At Diagnosis, During And After Completion Of Multidrug

Treatment" BR J OPHTHALMOL VOL: 91 (8) 2007 AUG.

P.1019-1022.

15.Daniel, Ebenezer Koshy, Sheena; Joseph, Geetha A; Rao, P S S

"Ocular Complications in Incident Relapsed Borderline

Lepromatous and Lepromatous Leprosy Patients in South India"

INDIAN J OPHTHALMOL VOL: 51 (2) 2003 JUN. P.155-159

16.Daniel, Ebenezer; Ebenezer, Gigi J and Job, Charles K "Pathology

of Iris in Leprosy" BR J OPHTHALMOLVOL: 81 (6) 1997 JUN.

P.490-492

17.De Soldenhoff, Richard "Ocular Leprosy" BR J OPHTHALMOL

VOL: 76 (7) 1992 JUL. P.447 Type: Letter

18.Ebenezer, G J; Daniel, E "Expression of Protein Gene Product 9.5

in Lepromatous Eyes Showing Ciliary Body Nerve Damage and a

"Dying Back" Phenomenon in the Posterior Ciliary Nerves" BR J

OPHTHALMOL VOL: 88 (2) 2004 FEB.P.178-181

19.Espiritu, Cesar G; Gelber, Robert and Ostler, H Bruce "Chronic

Anterior Uveitis in Leprosy: an insidious cause of blindness" BR J

OPHTHALMOL VOL: 75 (5) 1991 MAY P.273-275

20.FFYTCHE T J "Role of iris changes as a cause of blindness in

lepromatous leprosy" BR J OPHTHALMOL VOL: 65 (4) 1981

APR. P.231-239

21.Ffytche, T J "The Continuing Challenge of Ocular Leprosy" BR J

OPHTHALMOL VOL: 75 (2) 1991 FEB. P.123-124

22. Ffytche, Timothy "Importance of Early Diagnosis in Ocular

Leprosy "BR J OPHTHALMOL VOL: 73 (12) 1989 DEC. P.939

Type: Editorial

23.Garg, S P; Kalra, V K and Verma, Lalit "Conjunctival Microbial

Flora in Leprosy" INDIAN J OPHTHALMOL VOL: 39 (2) 1991

APR. P.59-61

24. Gnanadoss, A Samuel; Rao, Srinivasa "Ocular Lesions in

Leprosy - A study" TNOA VOL: 42 (1) 2001 MAR. P.25-29.

25.Gupta, Alka; Mithal, Sandeep "Ocular Involement in Leprosy - A

Clinical Study" AFRO ASIAN J OPHTHALMOL VOL: 9 (2)

1990 SEP. P.64-67

26.Hieselaar, Laetitia C J M; Hogeweg, Margreet and De Vries,

Christina L"Corneaal Sensitivity in Patients with Leprosy and in

Controls" BR J OPHTHALMOL VOL: 79 (11) 1995 NOV.

P.993-995

27.Hogeweg, M; Keunen, J E E "Prevention of Blindness in Leprosy

and the Role of the Vision 2020 Programme" EYE VOL: 19 (10)

2005 OCT. P.1099-1105

28.Hogeweg, Margreet "The Continuing Challenge of Ocular Leprosy"

BR J OPHTHALMOL VOL: 76 (4) 1992 APR. P.254-255

Type: Letter

29.House, Philip H "Ocular Leprosy: a case report and discussion of the

pathology" AUST N Z J OPHTHALMOL VOL: 14 (1) 1986

FEB. P.59-63

30.Johnstone, Peter A S; George, Athanasius D and Meyers, Wayne M

"Ocular Lesions in Leprosy"ANN OPHTHALMOL VOL: 23(8)

1991 AUG. P.297-303

31. Karacorlu, Murat A Surel, Zeki; Cakiner, Tulay; Hanyaloglu,

Erdal ;Saylan, Turkan; Mat, Cem "Pupil Cycle Time and Early

Autonomic Involvement in Ocular Leprosy" BR J OPHTHALMOL

VOL: 75 (1) 1991 JAN. P.45-48

32. Karacorlu, Murat A; Cakiner, Tulay and Saylan, Turkan

"Corneal Sensitivity and Correlations between Decreased Sensitivity

and Anterior Segment Pathology in Ocular Leprosy" BR J

OPHTHALMOL VOL: 75 (2) 1991 FEB. P.117-119.

33.Kundu, S K "An Indigenous Drug in the Treatment of Acute

Iridocyclitis in Leprosy Patients: a study in 13 patients" INDIAN

J OPHTHALMOL VOL: 20 (1) 1972 MAR. P.23-24

34.LAMBA P A; KUMAR Santosh "Ocular involvement from leprosy"

INDIAN J OPHTHALMOL VOL: 32 1984 MAR. P.61

35.Lamba, P A; Srinivasan, Renuka and Rohatgi, Jolly "Surgical

Management in Ocular Leprosy" INDIAN J OPHTHALMOL VOL:

35 (3) 1987 MAY P.153-157

36.Lewallen, Susan Tungpakorn, Narong C; Kim, Sung-Hwa ;

Courtright,Paul "Progression of Eye Disease in "cured" Leprosy

Patients: Implications for understanding the pathophysiology of

ocular disease and for addressing eyecare needs" BR J

OPHTHALMOL VOL: 84 (8) 2000 AUG. P.817-821

37.Lewallen, Susan; Courtright, paul "A overview of Ocular Leprosy

after 2 Decades of Multidrug Therapy" INT OPHTHALMOL CLIN

VOL: 47 (3) 2007 SUM. P.87-101

38.Lewallen, Susan; Courtright, Paul and Lee, Ho-Sung "Ocular

Autonomic Dysfunction and Intraocular Pressure in Leprosy " BR J

OPHTHALMOL VOL: 73 (12) 1989 DEC. P.946-949

39.Malaty, Raga; Togni, Birgitta "Corneal Changes in Nine-Banded

Armadillos with Leprosy" INVEST. OPHTHALMOL. VIS. SCI.

VOL: 29 (1) 1988 JAN. P.140-145 Type: Report

40.Marmor, Michael F "History of Ophthalmology: The Ophthalmic

Trials of G.H.A. Hansen" SURV OPHTHALMOL VOL: 47 (3)

2002 MAY-JUN. P.275-287

41. Mithal, Sandeep Pratap, V K; Gupta, Alka; Rajiv "Clinico-

Histopathological Study of the Eye in Leprosy" INDIAN J

OPHTHALMOL VOL: 36 (3) 1988 JUL. P.135-139.

42.Prasad, V N Narain, Mool; Mikhija, R D; Pandey, O N "Cataract

Surgery in Leprosy Patients"AFRO ASIAN J OPHTHALMOL

VOL: 5 (2) 1986 SEP. P.94-97

43.RADHAKRISHNAN N; ALBERT Sathia "Blindness due to

leprosy"INDIAN J OPHTHALMOL VOL: 28 (1) 1980 APR. P.19

44.Rathianm, S R; Khazaei, Hadi M "Histopathological Study of

Ocular Erythema Nodosum Leprosum and Post-Therapeutic Scleral

Perforation: a case report" INDIAN J OPHTHALMOL VOL: 56

(5) 2008 SEP. P.417-419

45.Rathinam, S R; Khazaei, Hadi "Histopathological Study of Ocular

Erythema Nodosum Leprosum and Post-Therapeutic Scleral

Perforation: a case Report" INDIAN J OPHTHALMOL VOL: 56

(4) 2008 AUG. P.417-419

46.Rathinam, S; Prajna, L "Hypopyon in Leprosy Uveitis" J

POSTGRAD MED VOL: 53 (1) 2007 JAN. P.46-47 Type:

Reprint

47.Richards, William W "Feature Photo: Ocular Leprosy" ARCH

OPHTHAL VOL: 93 (8)1975 AUG. P.696 Allen, James H; Jerome

L Byers "The Pathology of Ocular Leprosy" ARCH OPHTHAL

VOL: 64 (2) 1960 AUG. P.216

48.Sanjiv, Desai Rajiv, Desai; Desai, N C; Shoba, Lohiya; Kumar, K

"Ocular Findings in the Inmates of a Leprosy Rehabilitation Centre"

INDIAN J OPHTHALMOL VOL: 37 (2) 1989 APR.-JUN. P.96-97

49.SATYANARAYANA C "Ocular manifestations of

leprosy"OPHTHALMIC VIEWS AND NEWS VOL: 4 (4) 1987

OCT. P.115

50. Saxena, R C "Ocular Involvement in Leprosy" INDIAN J

OPHTHALMOL VOL: 11 (1) 1963 APR. P.13-16.

51.SEARS Marvin L "Ocular leprosy" AM. J. OPHTHALMOL VOL:

46 (3- PT.1) 1958 SEP. P.359

52.SHIELDS Jerry A "Ocular findings in leprosy" AM. J.

OPHTHALMOL VOL: 77 (6) 1974 JUN. P.880

53.Singhi, Mahendra K; Kacchawa, Dilip and Ghiya, Bhikam C

"Ocular Involvement in Leprosy" INDIAN J OPHTHALMOL VOL:

50 (4) 2002 DEC. P.355-356 Type: Letter

54.SLEM Gulhan "Clinical studies of ocular leprosy" AM. J.

OPHTHALMOL VOL: 71 (1) 1971 JAN. P.431

55.SRINIVASAN H "Lagophthalmos and its correction in leprosy

patients" TNOA VOL: 7 (3) 1970 MAY P.97

56. TAYLOR J "The eye in leprosy" TNOA VOL: 14(3)1977

May P.91

57.Thomas, Ravi; Thomas, Saju and Muliyil, Jayaprakash "Prevalence

of Glaucoma in Treated Multibacillary Hansen Disease" J

GLAUCOMA VOL: 12 (1) 2003 FEB. P.16-22

58. Thompson, K J "The Changing Face of Leprosy: still a cause

of preventable blindness" BR J OPHTHALMOL VOL: 90 (5) 2006

MAY P.528-529 Type: Editorial.

59. Waddell, Keith M; Paul, R Saunderson "Is Leprosy Blindness

Avoidable: the effect of disease type, duration, and treatment on eye

damage from leprosy in Uganda" BR J OPHTHALMOL VOL: 79

(3) 1995 MAR. P.250-256.

60. Whitcher, John P; Srinivasan, M "Leprosy - A New Look at

an Old Disease" BR J OPHTHALMOL VOL: 84 (8) 2000 AUG.

P.809-810 Type: Editorial.

61. Yuen, Hunter K L; Liu, David T L and Lam, Dennis S C

"Corneal Leproma as an Initial Feature of Lepromatous Leprosy"

ARCH OPHTHAL VOL: 124 (11) 2006 NOV. P.1661-1662

Type: Photo Essay.

ABBREVIATIONS

AFB ACID FAST BACILLAICBC COMPLETE BLOOD COUNTENL ERYTHEMA NODOSUM LEPROSUMG6PD GLUCOSE -6 PHOSPHATASE DEHYDROGENASEHLA HUMAN LEUCOCYTE ANTIGENIG IMMUNOGLOBULINKP KERATIC PRECIPITATESLL LEPROMATOUS LEPROSYMB MULTI BACILLARYMDT MULTI DRUG THERAPYM.LEPRAE MYCROBACTERIUM LEPRAETT TUBERCULOID LEPROSYTNF TUMOUR NECROSIS FACTORWHO WORLD HEALTH ORGANISATIONNLEP NATIONAL LEPROSY ERADICATION PROGRAMMENLCP NATIONAL LEPROSY CONTROL PROGRAMME

LAGOPHTHALMOS – RE

LATERAL TARSORRAPHY - RE

MULTI BACILLARY BLISTER PACK

PAUCI BACILLARY BLISTER PACK

KOEPPE’S NODULES

PHTHISIS BULBI

SADDLE NOSE DEFORMITY

TRICHIASIS - UPPER LID

EPISCLERITIS

BROKEN POSTERIOR SYNECHIAE

IRIDOCYCLITIS WITH HYPOPYON

IRIS – SPHINCTER PUPILLAE ATROPHY

IRIS – ATROPHIC PATCHES

CORNEAL ULCER WITH HYPOPYON